Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival
Scaffold-attachment-factor A (SAFA) has important roles in many normal and pathologic cellular processes but the scope of its function in cancer cells is unknown. Here, we report dominant-negative activity of novel peptides derived from the SAP and RGG-domains of SAFA and their effects on proliferat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.621825/full |
| _version_ | 1818662653990535168 |
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| author | Pavan Kumar Puvvula Anne M. Moon Anne M. Moon Anne M. Moon |
| author_facet | Pavan Kumar Puvvula Anne M. Moon Anne M. Moon Anne M. Moon |
| author_sort | Pavan Kumar Puvvula |
| collection | DOAJ |
| description | Scaffold-attachment-factor A (SAFA) has important roles in many normal and pathologic cellular processes but the scope of its function in cancer cells is unknown. Here, we report dominant-negative activity of novel peptides derived from the SAP and RGG-domains of SAFA and their effects on proliferation, survival and the epigenetic landscape in a range of cancer cell types. The RGG-derived peptide dysregulates SAFA binding and regulation of alternatively spliced targets and decreases levels of key spliceosome proteins in a cell-type specific manner. In contrast, the SAP-derived peptide reduces active histone marks, promotes chromatin compaction, and activates the DNA damage response and cell death in a subset of cancer cell types. Our findings reveal an unprecedented function of SAFA-derived peptides in regulating diverse SAFA molecular functions as a tumor suppressive mechanism and demonstrate the potential therapeutic utility of SAFA-peptides in a wide range of cancer cells. |
| first_indexed | 2024-12-17T05:04:23Z |
| format | Article |
| id | doaj.art-e3e2695435604615928c7489343e3037 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T05:04:23Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e3e2695435604615928c7489343e30372022-12-21T22:02:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.621825621825Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and SurvivalPavan Kumar Puvvula0Anne M. Moon1Anne M. Moon2Anne M. Moon3Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, PA, United StatesDepartment of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, PA, United StatesDepartment of Human Genetics, University of Utah, Salt Lake City, UT, United StatesThe Mindich Child Health and Development Institute, Hess Center for Science and Medicine at Mount Sinai, New York, NY, United StatesScaffold-attachment-factor A (SAFA) has important roles in many normal and pathologic cellular processes but the scope of its function in cancer cells is unknown. Here, we report dominant-negative activity of novel peptides derived from the SAP and RGG-domains of SAFA and their effects on proliferation, survival and the epigenetic landscape in a range of cancer cell types. The RGG-derived peptide dysregulates SAFA binding and regulation of alternatively spliced targets and decreases levels of key spliceosome proteins in a cell-type specific manner. In contrast, the SAP-derived peptide reduces active histone marks, promotes chromatin compaction, and activates the DNA damage response and cell death in a subset of cancer cell types. Our findings reveal an unprecedented function of SAFA-derived peptides in regulating diverse SAFA molecular functions as a tumor suppressive mechanism and demonstrate the potential therapeutic utility of SAFA-peptides in a wide range of cancer cells.https://www.frontiersin.org/articles/10.3389/fonc.2021.621825/fullhnRNPUepigeneticscell-penetrating peptidessplicingcancerRGG domain |
| spellingShingle | Pavan Kumar Puvvula Anne M. Moon Anne M. Moon Anne M. Moon Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival Frontiers in Oncology hnRNPU epigenetics cell-penetrating peptides splicing cancer RGG domain |
| title | Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival |
| title_full | Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival |
| title_fullStr | Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival |
| title_full_unstemmed | Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival |
| title_short | Novel Cell-Penetrating Peptides Derived From Scaffold-Attachment- Factor A Inhibits Cancer Cell Proliferation and Survival |
| title_sort | novel cell penetrating peptides derived from scaffold attachment factor a inhibits cancer cell proliferation and survival |
| topic | hnRNPU epigenetics cell-penetrating peptides splicing cancer RGG domain |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.621825/full |
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